This project examines information flow in the mammalian taste bud, and in particular analyzes how sour (acid) taste is processed in these peripheral sensory organs. The Specific Aims examine the notion that sour taste is handled in a fundamentally different manner than is sweet, bitter or umami taste. Specifically, the experiments test the hypotheses that (a) sour taste is transduced primarily by intracellular stimuli (protons) and (b) serotonin and norepinephrine are neurotransmitters involved in sour taste signaling in taste buds. The first Specific Aim deals with transduction mechanisms. Sour taste transduction has received a surge of interest following the identification of acid-sensitive TRP-like channels that are expressed in taste cells, PKD2L1 and PKD1L3. These channels have been postulated as the mechanism for sour taste. Curiously, one of the key observations in sour taste is that the proximate stimulus appears to be intracellular acidification. This grant describes experiments designed to extend and test the role of PKD channels in sour taste and explore how and whether cytosolic acidification activates acid-sensing taste transduction channels. The remaining three Specific Aims focus on how signals for sour taste are processed in taste buds, and specifically explore the model that there are two classes of chemoresponsive taste cells in the mammalian taste bud: (a) Type II receptor cells and (b) Type III presynaptic cells. These different cell types may respond to different classes of taste stimuli and encode taste signals in fundamentally different manners. Specifically, aminergic Type III presynaptic cells appear to be responsible for sour taste. The health relevance for understanding sour (acid) taste includes its role in stimulating swallowing in patients experiencing oropharyngeal dysphagia. Swallowing disorders can result from head and neck cancer or from a host of neurological problems and can occur in all age groups, from newborn to the elderly. Furthermore, oropharyngeal swallowing disorders are seriously debilitating. Yet despite the finding that sour taste stimuli can facilitate swallowing in these patients, virtually nothing is known about how sour taste elicits this reflex. If sour taste is linked with bioaminergic synaptic mechanisms, as will be explored in this proposal, this may open the way for new therapies for some types of oropharyngeal dysphagia. A further health relevance is that the studies on acid taste mechanisms may shed light on pain transduction. Inflammatory tissue acidosis is a major cause of pain. Although much is known about how extracellular protons stimulate nociceptors, little attention to date has been paid to intracellular acidification, even though this likely occurs during inflammation. PUBLIC HEALTH RELEVANCE The health relevance for understanding sour taste includes its role in stimulating swallowing in patients experiencing oropharyngeal dysphagia. Despite the finding that sour taste stimuli can facilitate swallowing in these patients, virtually nothing is known about how sour taste elicits this reflex. If sour taste is linked with aminergic synaptic mechanisms, as will be explored in this proposal, this may open the way for new therapies for some types of oropharyngeal dysphagia. Secondarily, understanding acid taste transduction may shed light on pain mechanisms associated with inflammation and tissue acidosis. [unreadable] [unreadable] [unreadable]